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A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model
| Item Type: | Preprint |
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| Title: | A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model |
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| Creators Name: | Kreye, J. and Reincke, S.M. and Kornau, H.C. and Sanchez-Sendin, E. and Corman, V.M. and Liu, H. and Yuan, M. and Wu, N.C. and Zhu, X. and Lee, C.C.D. and Trimpert, J. and Hoeltje, M. and Dietert, K. and Stoeffler, L. and von Wardenburg, N. and van Hoof, S. and Homeyer, M.A. and Hoffmann, J. and Abdelgawad, A. and Gruber, A.D. and Bertzbach, L.D. and Vladimirova, D. and Li, L.Y. and Barthel, P.C. and Skriner, K. and Hocke, A.C. and Hippenstiel, S. and Witzenrath, M. and Suttorp, N. and Kurth, F. and Franke, C. and Endres, M. and Schmitz, D. and Jeworowski, L.M. and Richter, A. and Schmidt, M.L. and Schwarz, T. and Mueller, M.A. and Drosten, C. and Wendisch, D. and Sander, L.E. and Osterrieder, N. and Wilson, I.A. and Pruess, H. |
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| Abstract: | The emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from ten COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb CV07-209 neutralized authentic SARS-CoV-2 with IC(50) of 3.1 ng/ml. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 A revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2 neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy. |
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| Keywords: | Animals, Hamsters |
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| Source: | bioRxiv |
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| Publisher: | Cold Spring Harbor Laboratory Press |
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| Article Number: | 2020.08.15.252320 |
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| Date: | 16 August 2020 |
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| Official Publication: | https://doi.org/10.1101/2020.08.15.252320 |
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